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Biomedical subjects

D Schenk

Publications and source records attributed to D Schenk.

At least 55 records · Page 3Linked to original sources
PubMed1992

Kunitz protease inhibitor-containing amyloid beta protein precursor immunoreactivity in Alzheimer's disease.

The amyloid beta protein (beta/A4) that is deposited in senile plaques and in cerebral vessels in Alzheimer's disease (AD) is derived from a larger membrane-associated glycoprotein, the amyloid beta protein precursor (APP). The gene encoding APP produces at least four major transcripts. Three of the four transcripts contain an alternatively-spliced exon encoding a Kunitz protease inhibitor domain (KPI). We now report the results of a series of experiments using novel immunohistochemical reagents to anatomically localize beta/A4, APP, and KPI-containing forms of APP (APP-KPI) in the hippocampal formation and temporal neocortex. A new monoclonal antibody against beta/A4 recognized senile plaques and vascular amyloid, but no cellular elements. Anti-APP and anti-KPI monoclonal antibodies stained neurons, including proximal axons and dendrites. The neuritic component of some plaques in patients with AD and in elderly control individuals were also immunoreactive for both APP and APP-KPI. Quantitative assessment of senile plaques in temporal neocortex showed that, on average, about one-third of beta/A4 immunoreactive plaques stained with either anti-APP or anti-KPI. Amyloid beta protein precursor and APP-KPI immunoreactivity were also found in the white and grey matter vessels of both AD patients and control individuals. These results suggest that KPI-containing forms of APP are present in dystrophic neurites of senile plaques, and normally in neurons, neuronal processes, and in the vascular compartment in the brain. Thus, APP-KPI is in a position to be intimately associated with beta/A4 deposition in the neuropil, in plaques and in amyloid angiopathy.

Adult↗
PubMed1989

Recombinant expression of a secreted form of the atrial natriuretic peptide clearance receptor.

A general structure for the atrial natriuretic peptide clearance receptor (ANP C-receptor) has been proposed based on hydropathicity analysis of the deduced amino acid sequence of this membrane protein (Fuller, F., Porter, J.G., Arfsten, A., Miller, J., Schilling, J., Scarborough, R.M., Lewicki, J.A., and Schenk, D.B. (1988) J. Biol. Chem. 263, 9395-9401). The ANP C-receptor is believed to possess a large amino-terminal extracellular domain (436 amino acids), a single hydrophobic transmembrane anchor (23 amino acids), and a short cytoplasmic tail (37 amino acids). As a means of testing the structure and proposed cellular orientation of this protein, we have employed the technique of in vitro mutagenesis to prepare a receptor mutant (anc-) lacking the transmembrane and cytoplasmic domains. Expression of this mutant in mammalian cells using a vaccinia virus vector results in secretion of a truncated soluble form of the ANP C-receptor which binds native ANP and synthetic ANP analogs with a specificity similar to that of the native ANP C-receptor. In contrast to the native ANP C-receptor that exists predominantly as a homodimer on the cell surface, the secreted receptor exists as a monomeric species. The results are consistent with the proposed structure of this receptor with the amino-terminal domain containing the ANP-binding site oriented extracellular to the plasma membrane. In addition, these data demonstrate that the receptor does not require association with the plasma membrane or its native dimeric configuration in order to bind ANP ligands with high affinity and specificity.

Amino Acid Sequence↗
PubMed1989

The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjects.

The 4.2-kilodalton (kDa) polypeptide associated with the cerebral amyloid deposits of Alzheimer's disease (AD) derives from a much larger protein that is encoded by a gene on chromosome 21. In the present study, we have used antibodies raised against portions of the amyloid protein precursor (APP) to map its normal distribution and to gain further insights into the events that lead to amyloid deposition. Antibodies raised against several different portions of APP reacted with proteins having apparent molecular sizes of 65, 67, and 132 kDa on Western blots. In sections through the normal human brain, immunocytochemistry revealed punctate concentrations of the protein in pyramidal cells of the neocortex, particularly in associative regions, and intense staining in the CA1 pyramidal cells of the hippocampus. By electron microscopy, this punctate distribution coincided with dense concentrations of the protein in secondary lysosomes. In the hippocampus of several AD cases examined, abnormally dense immunostaining in enlarged intracellular domains accompanied a severe atrophy of the CA1 neurons. These data suggest that accumulations of APP in lysosomes of particular neurons may, in AD, lead to proteolytic events that form the insoluble 4.2-kDa amyloid peptide.

Aged↗
PubMed1986

Atrial natriuretic peptide mRNA is regulated by glucocorticoids in vivo.

In these studies glucocorticoids were found to increase the plasma levels of atrial natriuretic peptide (ANP) as well as the expression of the ANP gene in the Sprague-Dawley rat. Plasma ANP rose two-fold after 48 hrs. of exposure to dexamethasone (1 mg/day) in both intact and adrenalectomized animals. This was accompanied by a 1.5-2.0 fold increase in the levels of atrial and ventricular ANP transcripts. Deoxycorticosterone acetate (5 mg/day), administered on the same schedule, failed to increase either plasma ANP levels or cardiac ANP mRNA accumulation. These effects suggest that ANP may have a potential role as a mediator of glucocorticoid activity in the cardiovascular system and support the hypothesis that ANP is a glucocorticoid-regulated gene.

Animals↗
PubMed1982

Comparison of the antigenicity and tolerance of an influenza aluminium oxide adsorbate vaccine with an aqueous vaccine.

A randomized trial was carried out in 189 adult subjects to test the antigenicity and tolerance of two experimental influenza vaccines, one adsorbed onto aluminium oxide and the other one aqueous, with equal antigen contents. Blood samples for antibody assays, using the haemagglutination inhibition test and the neuraminidase inhibition test, were taken before and 30, 90 and 180 days after vaccination. The results showed that the adsorbate influenza vaccine had a superior immunogenic action to the aqueous vaccine at the same dose rate. There were no significant differences between the tolerances of the two vaccines, which were injected with a needle. About 81% of the vaccinated subjects showed no subjective or objective signs of intolerance. Systemic reactions, which were reported by 9% of the vaccinated subjects, were verified by the doctor in only 2% of cases.

Adolescent↗